Aging Us
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Elimination of senescent cells (SnC) is anti-atherogenic, but the specific contribution of senescent vascular endothelial cells (EC) is unknown. We inactivated angiopoietin like-2 (angptl2), a marker of SnEC and a pro-atherogenic cytokine in LDLr-/-, hApoB100+/+ atherosclerotic (ATX) mice. Three months after a single vascular delivery of a small hairpin (sh)Angptl2 in 3-month old ATX mice using an adeno-associated virus serotype 1 (AAV1), aortic atheroma plaque progression was slowed by 58% (p<0.0001). ⋯ Four weeks post-injection, the endothelial progenitor marker Cd34 increased, suggesting endothelial repair. In arteries of atherosclerotic patients, we observed a strong correlation between p21 and ANGPTL2 (r=0.727, p=0.0002) confirming the clinical significance of angptl2-associated senescence. Our data suggest that therapeutic down-regulation of vascular angptl2 leads to the clearance of SnEC by apoptosis, stimulates endothelial repair and reduces atherosclerosis.
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Recently, increasing evidence has uncovered the roles of mRNA-miRNA-lncRNA network in multiple human cancers. However, a systematic mRNA-miRNA-lncRNA network linked to pancreatic cancer prognosis is still absent. ⋯ In a word, we established a novel mRNA-miRNA-lncRNA sub-network, among which each RNA may be utilized as a prognostic biomarker of pancreatic cancer.
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Non-small cell lung cancer (NSCLC) is the most common and lethal human malignant tumor worldwide. Platinum-based chemotherapy is still the mainstay of treatment for NSCLC. However, long-term chemotherapy usually induces serious drug resistance in NSCLC cells. ⋯ Furthermore, we demonstrated that the downregulation of miR-204 expression was responsible for CAV-1 overexpression in these cisplatin-resistant NSCLC cells. We then found that enforced expression of miR-204 can resensitize CR-A549 and CR-PC9 cells to cisplatin-induced mitochondrial apoptosis through suppression of the caveolin-1/AKT/Bad pathway. We demonstrated that dysregulation of miR-204/caveolin-1 axis is an important mechanism for NSCLC cells to develop the chemoresistance.
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Renal dysfunction is a risk factor for morbidity and mortality in cardiac surgery patients. Serum Cystatin C (sCysC) is a well-recognized marker of early renal dysfunction but few reports evaluate its prognostic cardio-vascular role. The aim of the study is to consider the prognostic value of sCysC for cardiovascular mortality. ⋯ In multivariate CPHM, the only significant predictors of mortality were sCysC (p<0.00001, risk ratio: 1.529, CI: 1.29-1.80) and age (p=0.039, risk ratio: 1.019, CI: 1.001-1.037). When replacing sCysC with sCrea, the only significant predictor of mortality was sCrea (p=0.0026; risk ratio 1.20; CI: 1.06-1.36). Increased levels of sCysC can be considered a useful biomarker of cardiovascular mortality in cardiac-surgery patients.
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Critically ill cirrhotic patients with acute kidney injury (AKI) are associated with high mortality rates. The aims of this study were to develop a specific prognostic score for critically ill cirrhotic patients with AKI, the acute kidney injury - Chronic Liver Failure - Sequential Organ Failure- Assessment score (AKI-CLIF-SOFA) score. This study focused on 527 cirrhotic patients with AKI admitted to intensive care unit and constructed a new scoring system, the AKI-CLIF-SOFA, which can be used to prognostically assess mortality in these patient population. ⋯ The area under the receiver operating characteristic curve (auROC) of AKI-CLIF-SOFA scoring system was 0.74 in 30 days, 0.74 in 90 days, 0.72 in 270 days and 0.72 in 365 days. Additionally, this study demonstrated that the new model had more discriminatory power than chronic liver failure- sequential organ failure assessment score (CLIF-SOFA), SOFA, model for end stage liver disease (MELD), kidney disease improving global outcomes (KDIGO) and simplified acute physiology score II (SAPS II) (auROC: 0.72, 0.66, 0.64, 0.62, 0.63 and 0.65 respectively, all P < 0.05) for the prediction of the 365-days mortality. Therefore, AKI-CLIF-SOFA demonstrated a valuable discriminative ability compared with KDIGO, CLIF-SOFA, MELD, SAPS II and SOFA in critically ill cirrhotic patients with AKI.